The ultimate goal of this project is to find an agent that will cause a reversal of preneoplasia in epithelial tissue. Currently, the compounds being investigated are vitamin A and its analogs (retinoids). Emphasis has been placed on the metabolism of a natural retinoid, retinoic acid. It has been demonstrated that a hamster tracheal organ culture system will metabolize retinoic acid to more polar compounds that cochromatograph in several reverse phase high-pressure liquid chromatography systems with metabolites found in vivo in the hamster intestine and urine. A knowledge of the structure and the biological activity of the various naturally occurring metabolites of retinoic acid will help to decipher the biochemical mechanism of action of vitamin A in determining epithelial cell differentiation. It will also aid in designing analogs of vitamin A that will display biological activity in the reversal of preneoplasia and, at the same time, will show low toxicity in the animal.